Pros and Cons of Breast Cancer and Biomakers - Research Paper Example

?Pros and Cons of Breast Cancer and Biomarkers Introduction "Tumor markers or biomarkers are substances that are produced by cancer or by other cellsof the body in response to cancer or certain benign (noncancerous) conditions" (National Cancer Institute, 2012). Most of the tumor markers are produced by cancer cells and also normal cells, but are increased in cancerous conditions. These factors are found in tumor tissue, blood, urine and other tissues and fluids of the body in some patients with cancer. More often than not, tumor markers are proteins. (National Cancer Institute, 2012) More than 20 different tumor markers have been described and characterized and they are in clinical use (National Cancer Institute, 2012). While some are associated with only one type of cancer, others are associated with more than one type of cancer. However, there is no universal tumor marker that can detect any type of cancer. Tumor markers serve various purposes in cancer management like complementing diagnosis, prognostication, detection of recurrence, etc. However, there are certain limitations for the use of these markers. Thus, there are pros and cons to the use of tumor markers. In this essay, pros and cons of application of biomarkers or tumor markers in breast cancer management will be discussed. Application of breast cancer biomarkers The most common cancer affecting women all over the world is breast cancer and it has been estimated that about one million cases are diagnosed every year worldwide (Duffy et al, 2005). The main presenting features of the disease include lump in the breast, skin contour changes and nipple discharge. Asymptomatic cases may be picked up during routine screening tests. Definitive diagnosis is histopathology of the biopsy specimen. Several blood based biomarkers are available, but they do not have a role in the early diagnosis of the disease. For localized breast cancer, primary treatment is mastectomy or breast-conserving surgery and radiation. In invasive breast cancer, primary treatment is followed by hormone therapy or chemotherapy. These treatments have shown to reduce mortality related to breast cancer. Following primary therapy, the patients are followed up at regular intervals for surveillance. This includes clinical history, detailed physical examination, chest X-ray, mammography, biochemical testing and use of breast cancer markers. The intention is to detect recurrent disease at an early stage so that outcomes are better. This is one use of tumor marker. There are other uses of tumor markers in breast cancer management. Recurrent disease is common even in lymph node-negative cases and therapeutic options in such cases include exclusive hormone therapy or chemotherapy or a combination of both. Metastatic breast cancer is considered incurable and treatment is mainly palliative. Serial assessment of tumor markers is useful in to decide whether a particular treatment modality can be continues or there is a need to switch to another treatment modality. Thus, it is now clear that tumor markers are necessary for optimal management of breast cancer (Duffy et al, 2005). Pros of breast cancer biomarkers There are 2 types of tumor markers available for breast cancer and they are serum markers and tissue markers. Examples of serum markers useful in breast cancer include CEA, CA 15-3, polypeptide antigen or TPA, BR 27.29, tissue polypeptide specific antigen or TPS and the shed form of HER-2 (Duffy, 2006). Examples of tissue markers include urokinase plasminogen activator, HER-2, hormone receptors and plasminogen activator-1. Most of the oncological organizations in Europe, US and other countries recommend routine assay of progesterone and estrogen receptors on all newly diagnosed breast cancers to select the type of hormone therapy (Duffy, 2006). These markers are also useful to determine prognosis. HER-2 is also recommended on all newly diagnosed breast cancer cases. The main purpose of this is to determine whether the cancer is suitable for Trastuzumab (Herceptin). This test is performed in both early and advanced cancers. HER 2 is used to determine prognosis in conjunction with other prognosis factors. There is not much data on serum testing of HER-2. It may however be useful to monitor patients with advanced breast cancer on treatment with Trastuzumab. Plasminogen activator inhibitor 1 and urokinase plasminogen activator are independent prognostic factor of breast cancer, especially in lymph node negative cases. A combination of both these factors has been recommended for superior determination. Women with lymph node-negative breast cancer with marked elevation of both these markers must be treated with adjuvant chemotherapy. It is recommended to test for CA 15-3 routinely in asymptomatic patients with operable breast cancer. There is also some evidence that early initiation of therapy based on increasing levels of this marker improved treatment outcomes (Duffy, 2006). Potential uses of serum markers in breast cancer include "aiding early diagnosis, determining prognosis, prospectively predicting response or resistance to specific therapies, surveillance after primary surgery, and monitoring therapy in patients with advanced disease" (Duffy, 2006). Determination of prognosis is done by estimating tumor size and grade, lymph node status and tissue markers like HER-2, estrogen and progesterone receptors, plasminogen activator-1 and urokinase plasminogen activator. These need biopsy or surgical excision samples and hence are disadvantageous. In this regard, CA 15-3 is considered valuable in prognostication because it only needs a serum sample and there is evidence that estimation of this factor in preoperative state, and when combined with other pathological estimates provides real-time prognostic information. Other serum markers too have been evaluated in this regard and found to be useful for estimating prognosis, but in combination with other pathological attributes. S100P and ubiquitin are tow protein markers when used in combination can provide high discrimination between health breast tissue and breast cancer tissue (Chung et al, 2013). Cons of breast cancer biomarkers Application of tumor markers in breast cancer management has several disadvantages. Hormone receptors are weak predictors of patient outcome and do not have much role in lymph node-negative cases. Hence, they cannot be used alone to determine prognosis. One major disadvantage with tissue markers is that breast cancer sample is necessary and hence biopsy or surgery is necessary (Duffy, 2006). The role of serum tumor markers is not well established in breast cancer. The most widely used serum markers are carcinoembryonic antigen or CEA and CA 15-3. Other less widely used markers include tissue polypeptide antigen or TPA, BR 27.29, tissue polypeptide specific antigen or TPS and the shed form of HER-2. Lack of sensitivity and lack of specificity for early-stage disease precludes the use of currently available serum markers for early diagnosis of breast cancer (Steenkamer, 2012). CA 15-3, the most widely used marker alerts the physician about metastatic disease when there is a 5- 10 fold rise (Steenkamer, 2012). However, low concentration of the marker does not exclude metastasis. Another important aspect to be noted is that this tissue marker is actually not specific for breast cancer. Infact, increased values can be found even in healthy individuals, in certain conditions like liver disease and in other cancers like adenoarcinoma. Thus, mammography and histopathology are primary modalities for detection of early breast cancer. One of the main disadvantages with serum and tissue markers of breast cancer is that they lack specificity and also sensitivity to low volume disease. Thus, the currently available markers neither have a role in either screening or diagnosing early breast cancer (Duffy, 2005). The most widely used application of tumor marker is follow-up of patients diagnosed breast cancer. This clinical value is however unclear because of lack of appropriate data from randomized control trials (Duffy et al, 2005). So far, none of the available markers has been proven to be increased in all patients with breast cancer even in cases of advanced cancer. CA 15-3 is one useful marker, but even that is not specific and sensitive. In the absence of increased CA 15-3 concentrations, other serum markers may be useful for the purpose of monitoring, but even for them there is not much evidence in literature. Markers which are sensitive for determining and detecting distant metastases have little value in diagnosing recurrences in locoregional cancer recurrences (Duffy et al, 2005). There is no clear data about critical change in successive marker concentrations. There can exist paradoxical concentration of tumor markers after initiation of chemotherapy due to tumor cell necrosis or medicine related apoptosis. Certain tumor markers can increase even in other conditions like cirrhosis of liver, sarcoidosis, chronic active hepatitis, hypothyroidism and megaloblastic anemia (Duffy et al, 2005). Conclusion Biomarkers are useful in the management of patients with breast cancer. There are basically 2 types of biomarkers, serum and tissue. These help in calculating prognosis, determining the best modality of treatment and detecting recurrence in early stages. But the markers are not completely reliable because of lack of specificity and sensitivity. Certain other disadvantages include sampling necessity in tissue markers and paradoxical levels after chemotherapy. Thus, biomarkers can be used only in conjunction with traditional methods of patient surveillance like clinical history, physical examination and mammography. References American Cancer Society. (2012). The drawbacks of tumor markers. Retrieved on 13th April, 2013 from http://www.cancer.org/treatment/understandingyourdiagnosis/examsandtestdescriptions/tumormarkers/tumor-markers-drawbacks-of-t-m Chung, L., Shibli, S., Moore, K., et al. (2013). Tissue biomarkers of breast cancer and their association with conventional pathologic features. British Journal of Cancer, 108, 351–360. Retrieved on 13th April, 2013 from http://www.nature.com/bjc/journal/v108/n2/full/bjc2012552a.html Duffy, M.J., Esteva, F.J., Harbeck, N., Molina, R., Hayes, D.F. ( 2005). National Academy of Clinical Biochemistry Guidelines for the Use of Tumor Markers in Breast Cancer. NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic Breast Cancer. Duffy, M.J. (2005). Predictive Markers in Breast and Other Cancers: A Review. The American Association for Clinical chemistry. Retrieved on 13th April, 2013 from www.clinchem.org/content/51/3/494.full Duffy, M.J. (2006). Serum Tumor Markers in Breast Cancer: Are They of Clinical Value? Clinical Chemistry, 52 (3), 345-351. National Cancer Institute. (2012). Tumor Markers. Retrieved on 13th April, 2013 from http://www.cancer.gov/cancertopics/factsheet/detection/tumor-markers Steenkamer, M. (2012). Predictive markers for chemotherapy response in breast cancer. Master thesis for Cancer Genomics and Developmental Biology, Utrecht University, the Netherlands. Retrieved on 13th April, 2013 from https://docs.google.com/viewer?a=v&q=cache:FvNlign2c34J:igitur-archive.library.uu.nl/student-theses/2012-0831-200640/Thesis_MJSteenkamer_final.pdf+disadvantages+of+breast+cancer+markers&hl=en&gl=in&pid=bl&srcid=ADGEESjMrcvpsldEDgszBLMlxCLgNWyKoBZgXCGPFDSTbX86O2429IgkHk3QgKrW3R8Uya7kKOp-yyHckH1AsALzMKem5ECSY4Iq6etwhzVaYnO_e6QN9TAoZaEKgmw5xD-4gQrVdpgp&sig=AHIEtbSndu5OTN-IMfyncdBZi281BE_eew Read More